Clinical Guidance

No clinically relevant genotype-phenotype correlations for AMER1 have been confirmed. Initial reports of truncating variants at the 5' end of AMER1 predicting a severe phenotype have been disproven .

Source: GeneReviews — "Osteopathia Striata with Cranial Sclerosis"

Penetrance

Penetrance appears to be 100%, albeit with variable expressivity and severity of the phenotype, even within families.

Source: GeneReviews — "Osteopathia Striata with Cranial Sclerosis"

Diagnostic Criteria

No consensus clinical diagnostic criteria for osteopathia striata with cranial sclerosis (OS-CS) have been published, however the combination of macrocephaly, cranial sclerosis, and longitudinal metaphyseal striations of the long bones are considered highly characteristic of this condition.

Suggestive Findings

OS-CS should be suspected in individuals with the following clinical and radiographic findings.

Females and Mosaic and/or Mildly Affected Males

Clinical findings

Source: GeneReviews — "Osteopathia Striata with Cranial Sclerosis"

Differential Diagnosis

Females and mildly affected males. Disorders that may present with sclerotic bone disease similar to that observed in females (and mildly affected males) with osteopathia striata with cranial sclerosis (OS-CS) are summarized in . See also the Nosology of Genetic Skeletal Disorders: 2023 Revision, Group 24 – Osteopetrosis and related osteoclast disorders and Group 25 – Osteosclerotic disorders for a review of additional disorders that may be considered in the differential diagnosis of OS-CS. Males with a severe phenotype present with a multiple-malformation syndrome, usually without metaphyseal striations, making the differential diagnosis very broad. AMER1 should be included within the gene list for any fetal or neonatal multiple-malformation presentation. Table 3. Genes of Interest in the Differential Diagnosis of Osteopathia Striata with Cranial Sclerosis

Management Guidelines

No consensus clinical diagnostic criteria for osteopathia striata with cranial sclerosis (OS-CS) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with OS-CS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Osteopathia Striata with Cranial Sclerosis

Source: GeneReviews — "Osteopathia Striata with Cranial Sclerosis"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Osteopathia Striata with Cranial Sclerosis"

Surveillance Guidelines

Table 6.

Recommended Surveillance for Individuals with Osteopathia Striata with Cranial Sclerosis

System/Concern | Evaluation | Frequency

Musculoskeletal

| Clinical assessment for scoliosis joint contractures | Annually or as indicated

Hearing

| Audiology eval

Vision

| Ophthalmology eval

Cognition

| Developmental assessment

Wilms tumor

| Abdominal ultrasound | Every 3 mos until age 7 yrs as per Beckwith-Wiedemann syndrome guidelines until OS-CS specific guidelines are established1

1. The association of OS-CS with Wilms tumor has only recently been established . Until there is an evidentiary base for OS-CS-specific surveillance guidelines, surveillance based on Beckwith Wiedemann syndrome guidelines is recommended [; ; Author, personal communication with Professor Stephen Robertson].

Source: GeneReviews — "Osteopathia Striata with Cranial Sclerosis"